Researchers
have discovered a genetic mutation in the typhoid fever bacterium that
allows the organism to establish persistent infections in mice. The mutation
results in a greater production of the virulence proteins necessary to
infect host cells. The finding suggests that a single protein may be critical
in determining whether an infected individual develops a short-term illness
or becomes a carrier of the disease.

Typhoid fever occurs almost exclusively in developing countries and can
be treated with antibiotics. Left untreated, however, the disease can
persist for several months and sometimes becomes chronic. Chronic carriers
experience no symptoms beyond their initial illness, but the bacteria
remain in their cells. Controlling typhoid fever is difficult in part
because carriers are unaware that they are 'shedding' live Salmonella
enterica bacteria. Some 16 million new infections occur per year.

Mark O. Clements, of the Karolinska Institute in Stockholm, Sweden, and
colleagues set out to understand the genetics of typhoid fever infections.
They analyzed two forms of the bacterium in miceone that causes
the acute disease, and another that produces carriers. In the gene that
codes for PNPase (polynucleotide phosphorylase), they discovered a single-letter
mutation that shortens the protein.

Microarray analysis showed that PNPase mutants expressed more virulence
factor proteins; these proteins help the bacterium trick host cells into
internalizing the organism. Once inside the host cell, the bacterium relies
on the proteins to reproduce.

The scientists concluded that PNPase normally represses the expression
of virulence factor proteins, so mutant strains reproduce faster and more
efficiently than normal strains. PNPase mutants may be better able to
resist the host organism's immune system and establish themselves permanently,
making the infected individual a carrier. The findings are published in
Proceedings of the National Academy of Sciences.

The healthy carrier state, which occurs in five percent of typhoid fever
patients, made its first United States appearance in an Irish immigrant
named Mary Mallon, better known as 'Typhoid Mary.' A food service worker,
Mallon broke out of forced isolation in 1907 and caused several typhoid
outbreaks. She infected 47 people with the disease, three of whom died.

Although she is often depicted as a malicious villain, Mallon may never
have received an adequate explanation for why she was confined. She probably
acted unintentionally, unable to believe that she could feel healthy and
still spread a disease.